Integrated analysis of environmental and genetic influences on cord blood DNA methylation in new-borns.

TitleIntegrated analysis of environmental and genetic influences on cord blood DNA methylation in new-borns.
Publication TypeJournal Article
Year of Publication2019
AuthorsCzamara D, Eraslan G, Page CM, Lahti J, Lahti-Pulkkinen M, Hämäläinen E, Kajantie E, Laivuori H, Villa PM, Reynolds RM, Nystad W, Håberg SE, London SJ, O'Donnell K, Garg E, Meaney MJ, Entringer S, Wadhwa PD, Buss C, Jones MJ, Lin DTS, MacIsaac JL, Kobor MS, Koen N, Zar HJ, Koenen KC, Dalvie S, Stein DJ, Kondofersky I, Müller NS, Theis FJ, Räikkönen K, Binder EB
Corporate AuthorsMajor Depressive Disorder Working Group of the Psychiatric Genomics Consortium
JournalNat Commun
Date Published2019 06 11
KeywordsCohort Studies, DNA, DNA Methylation, Epigenesis, Genetic, Female, Fetal Blood, Gene-Environment Interaction, Genotype, Humans, Infant, Newborn, Male, Pregnancy, Risk Factors

Epigenetic processes, including DNA methylation (DNAm), are among the mechanisms allowing integration of genetic and environmental factors to shape cellular function. While many studies have investigated either environmental or genetic contributions to DNAm, few have assessed their integrated effects. Here we examine the relative contributions of prenatal environmental factors and genotype on DNA methylation in neonatal blood at variably methylated regions (VMRs) in 4 independent cohorts (overall n = 2365). We use Akaike's information criterion to test which factors best explain variability of methylation in the cohort-specific VMRs: several prenatal environmental factors (E), genotypes in cis (G), or their additive (G + E) or interaction (GxE) effects. Genetic and environmental factors in combination best explain DNAm at the majority of VMRs. The CpGs best explained by either G, G + E or GxE are functionally distinct. The enrichment of genetic variants from GxE models in GWAS for complex disorders supports their importance for disease risk.

Alternate JournalNat Commun
PubMed ID31186427
PubMed Central IDPMC6559955
Grant ListS10 OD018164 / OD / NIH HHS / United States